Project Summary The main objective of this research is to use cardiac magnetic resonance imaging (MRI) after implantation of cardiac resynchronization therapy (CRT) for heart failure to provide very detailed and high-quality data regarding the impact of left ventricular (LV) pacing site characteristics on LV structure and function after CRT. We believe this work will provide insights into mechanisms of CRT response and nonresponse, as well as ways to improve CRT implementation. The importance of heart failure is characterized by the following statistics: at least 5 million people in the United States have heart failure, 2.5 million require hospitalization, and more than 500,000 are diagnosed with heart failure each year. As a result, this research is highly aligned with the mission of the National Heart, Lung, and Blood Institute to enhance the health of individuals with heart disease or at risk for heart disease so they can live longer and more fulfilling lives. CRT involves implantation of an advanced pacemaker/defibrillator attached to three wires in the heart designed to make unevenly pumping hearts contract more synchronously and effectively. Although CRT is very beneficial for many patients, nonresponder rates are typically 35-50% when implants are not guided by imaging, often because of suboptimal positioning of the pacing wires with respect to scar and mechanical activation. During the K23 award, the PI demonstrated how MRI characterization of scar with late gadolinium enhancement and strain with the DENSE (Displacement Encoding with Stimulated Echoes) method before could be used to identify optimal pacing sites, but direct MRI evaluation of the effect of LV pacing sites on LV remodeling after CRT had not been possible until just recently when a new generation of CRT defibrillators was approved for conditional use in the MRI environment in February 2016. A post-CRT cardiac MRI provides is quite valuable because it can provide highly detailed and reproducible data regarding LV structure and function using optimized pulse sequences for strain, volumes, wall thickness, synchrony, and scar. In this study, post-CRT MRI findings will be compared with pre-CRT MRI findings to show how the LV pacing lead location relative to mechanical activation and scar alters LV remodeling after CRT and provide additional insights regarding the optimal spatial relationship between LV lead position and scar in the heart. MRI results will be compared with echocardiography results, and the findings promise to demonstrate how these imaging modalities can be used together for the benefit of CRT patients. We will enroll 40 CRT patients who will have cardiac MRI, echocardiography, cardiopulmonary exercise testing, symptom assessment, and laboratory testing before and 6 months after CRT. The project is expected to have a high impact on the field and lead to important improvements in CRT implementation. This work will also facilitate the PI's progression to independence by providing important data for subsequent work on an MRI-guided clinical trial for CRT and the development of computational models for LV remodeling after CRT based on LV pacing lead placement. 1